Individuals who develop diseases in association with antibodies or T lymphocytes which react with self structures are said to have autoimmunity. One group of such diseases, known as idiopathic inflammatory myopathies, are characterized by chronic inflammation of muscle or myositis. Some of these diseases appear to be the result of environmental agents, perhaps picornaviruses, infecting individuals with certain genes which govern immune responses. We are studying the immunogenetics, environmental agents and pathogenesis of these human autoimmune disease. Specific projects include: 1) A study of the HLA and T cell receptor (TCR) genes associated with autoantibodies specific to myositis. Within the last 5 months, the laboratory was established and has been organized to allow HLA DQ-alpha gene typing. This has been performed by polymerase chain reactions using sequence-specific probes on DNA collected from over 160 myositis patients representing all the major clinical and autoantibody subgroups. As is in the case for HLA-DR, DW, and DQ, there appear to be significant associations of DQ-alpha alleles with each of the myositis-specific autoantibodies. Studies of the other HLA genes and TCR gene distribution are under development. 2) Studies of the epidemiology of myositis are underway attempting to associate clinical signs and symptoms, season of disease-onset and geographic location, and therapeutic responses in the different clinical and autoantibody subsets. A very large study of 212 patients has confirmed that strong associations of the above do exist and we are initiating a larger multicenter study across the nation to confirm these data.